Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin.

Journal Article

Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into how mutations in these genes may lead to circuit dysfunction in diseases such as autism.

Full Text

Duke Authors

Cited Authors

  • Singh, SK; Stogsdill, JA; Pulimood, NS; Dingsdale, H; Kim, YH; Pilaz, L-J; Kim, IH; Manhaes, AC; Rodrigues, WS; Pamukcu, A; Enustun, E; Ertuz, Z; Scheiffele, P; Soderling, SH; Silver, DL; Ji, R-R; Medina, AE; Eroglu, C

Published Date

  • January 2016

Published In

Volume / Issue

  • 164 / 1-2

Start / End Page

  • 183 - 196

PubMed ID

  • 26771491

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.11.034

Language

  • eng